This invention relates to the treatment of hyperlipoproteinemia and more particularly to the treatment of hyperlipoproteinemia in humans with a dichloroacetate salt.
Lipoproteins consist of lipid (cholesterol or triglyceride) bound to various proteins. They are synthesized by the liver, from which they are secreted into the circulation of the blood stream. The relative proportion of lipid and protein is variable, and thus their physicochemical properties differ. The greater the proportion of lipid, the less dense is the lipoprotein. Based on the lipid-to-protein ratio and, hence, on the density, liproproteins are classified as (from least to most dense):
1. chylomicra PA1 2. very low density lipoproteins (VLDL) PA1 3. low density lipoproteins (LDL) PA1 4. intermediate low density lipoproteins (ILDL) PA1 5. high density lipoproteins (HDL) PA1 Type I (increased chylomicra) PA1 Type IIa (increased LDL) PA1 Type IIb (increased LDL and VLDL) PA1 Type III (increased ILDL) PA1 Type IV (increased VLDL) PA1 Type V (increased chylomicra and VLDL) PA1 a is an integer from 1 to 2, inclusive; PA1 b is an integer from 1 to 2, inclusive.
Based, in part, on the relative abnormal increases in the various lipoproteins, the hyperlipoproteinemias have been characterized as:
The constituency of chylomicra is almost all triglycerides.
Types IIb and IV hyperlipoproteinemia are most prevalent in diabetics.
Type IIa hyperlipoproteinemia (familial hypercholesterolemia) is characterized by a high level of plasma cholesterol.
Persons with excessive amounts of cholesterol in the blood stream have a greater tendency to develop cardio-vascular diseases than persons with lower or normal levels of plasma cholesterol.
Persons with excess amounts of triglycerides in their blood stream have a greater tendency to develop pancreatitis than persons with normal levels of triglycerides.
The effects of the dichloroacetate ion on various aspects of intermediary metabolism have been studied extensively in several animal models. Among its metabolic effects, the dichloroacetate ion alters lipid metabolism in animals by inhibiting peripheral fatty acids and ketone body oxidation.
Furthermore, hyperglycemia has been reduced in animals having diabetes mellitus by treatment with alpha, alpha substituted acetic acid derivatives, including sodium dichloroacetate, as taught in U.S. Pat. No. 3,179,562, issued to Howard E. Hoffman et al on Apr. 20, 1965. The Hoffman et al patent also teaches the maintenance of glycosuria within normal limits in animals having diabetes mellitus by oral ingestion of a compound including the dichloroacetate ion.